Clinical Trial: Improving the Results of Bone Marrow Transplantation for Patients with Severe Congenital Anemias

This study is currently recruiting patients.

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by: Warren G Magnuson Clinical Center (CC)


People with severe congenital anemias, such as sickle cell anemia, thalassemia, and Diamond Blackfan anemia, have been cured with bone marrow transplantation (BMT). The procedure, however, is limited to children younger than the age of 16 because the risks are lower for children than for adults.

The purpose of this study is to explore the use of a BMT regimen that, instead of chemotherapy, uses a low dose of radiation, combined with two immunosuppressive drugs. This type BMT procedure is described as nonmyeloablative, meaning that it does not destroy the patient's bone marrow. It is hoped that this type of BMT will be safe for patients normally excluded from the procedure because of their age and other reasons.

To participate in this study, patients must be between the ages of 18 and 65 and have a sibling who is a well-matched stem-cell donor. Beyond the standard BMT protocol, study participants will undergo additional procedures. The donor will receive G-CSF by injection for five days; then his or her stem cells will be collected and frozen one month prior to BMT. Approximately one month later, the patient will be given two immune-suppressing drugs, Campath 1-H and Sirolimus, as well as a single low dose of total body irradiation and then the cells from the donor will be infused.

Prior to their participation in this study, patients will undergo the following evaluations: a physical exam, blood work, breathing tests, heart-function tests, chest and sinus x-rays, and bone-marrow sampling.

Condition Treatment or Intervention Phase
Congenital Hemolytic Anemia
Diamond-Blackfan Anemia
 Procedure: Radiotherapy
 Drug: Alemtuzumab (Campath® (Registered Trademark))
 Drug: Sirolimus (Rapamune® (Registered Trademark))
Phase II

MedlinePlus related topics:  Anemia;   Genetic Disorders

Study Type: Interventional
Study Design: Treatment, Safety/Efficacy

Official Title: Nonmyeloablative Allogeneic Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation For Severe Congenital Anemias Including Sickle Cell Anemia, Thalassemia, and Diamond Blackfan Anemia

Further Study Details: 

Expected Total Enrollment:  25

Study start: May 19, 2003

Nonmyeloablative allogeneic peripheral blood stem cell transplants are currently being investigated in phase I/II trials assessing engraftment, efficacy, and toxicity at a number of transplant centers. Preliminary data, including our own experience with over 100 patients, have shown a high rate of complete donor engraftment with a relatively low toxicity profile. The decreased risk of transplant-related complications associated with nonmyeloablative transplants expands eligibility to patients with nonmalignant hematological disorders curable by allogeneic transplantation; however, significant toxicity with current regimens persists including severe GVHD leading to significant morbidity and mortality. Moreover, mixed chimerism has been shown to be sufficient to induce clinical remissions in children with nonmalignant hematologic disorders undergoing conventional allogeneic transplantation. Therefore, newer regimens need to be developed that are more applicable to patients with non-malignant disorders in whom no graft vs. leukemia effect is needed, and where mixed chimerism is sufficient for disease amelioration.

In this protocol, we propose transplantation in patients with severe congenital anemias including sickle cell anemia (SCA), thalassemia, or Diamond Blackfan anemia (DBA), considered at high risk for complications from or ineligible for standard BMT, with allogeneic peripheral blood stem cells from an HLA identical sibling using a novel immunosuppressive regimen without myeloablation in an attempt to further decrease the transplant related morbidity/mortality. The low intensity nonmyeloablative conditioning regimen will consist of low dose radiation, Alemtuzumab (Campath® (Registered Trademark)) and Sirolimus (Rapamune® (Registered Trademark)) as a strategy to provide adequate immunosuppression to allow sufficient engraftment for clinical remission with a lower risk of graft versus host disease development. T-cell replete, donor-derived, granulocyte colony stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSC) will be used to establish hematopoietic and lymphoid reconstitution, with additional T-cell infusions in those patients with unstable engraftment.

The primary endpoint of this study is donor engraftment. Other end points include degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic graft versus host disease (GVHD), incidence of graft rejection, transplant related morbidity, as well as disease-free and overall survival.


Genders Eligible for Study:  Both


Patients with Hb SS, SC, or Sb-thalo at high risk for disease related mortality or morbidity as defined by having one or more of the following:
- a previous neurologic event (either symptomatic or found by imaging alone),
- more than 2 painful crises per year for the last 2 years each requiring hospitalization,
- a previous acute chest syndrome,
- evidence of renal damage as defined as having an elevated creatinine of 1.5x normal or a reduced creatinine clearance, which is still greater than 50% of normal,
- red cell alloimmunization,
- stage I or II sickle chest, (Stage I patients have normal oxygen saturation but 80% of predicted normal pulmonary function tests. Stage II patients also have normal oxygen saturation but 60% of predicted normal pulmonary function tests.)
- osteonecrosis of multiple joints
- pulmonary hypertension as measured by a TRV jet of greater than 2.5m/s
- having failed hydroxyurea, as defined by a failure to achieve a hematologic response and/or clinical response where clinical/hematologic response is defined as a significant decrease in the number of crises experienced after a 6 month trial or a 2-3 fold increase in the hemoglobin F level unless has renal insufficiency preventing hydroxyurea use, or indication for transplant is or includes a neurologic event.
Patients with transfusion dependent Diamond Blackfan anemia
Patients with Thalassemia with Class II or III Iron overload
Ages 18- 65
6/6 HLA matched family donor available
Ability to comprehend and willing to sign an informed consent
Negative Serum B-HCG
6/6 HLA identical family donor
Ages greater than or equal to 2 and weight greater than 18 kg (in so far that the weight difference between recipient and donor does not exceed a reasonable likelihood of being able to obtain an adequate cell dose from the donor within two aphereses
Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive and no history of stroke)
Ability to comprehend and willing to sign an informed consent; assent obtained from minors
(any of the following would exclude the subject from participating)
Age less than 18 years or greater than 65 years
ECOG performance status of 3 or more.
Diffusion capacity of carbon monoxide (DLCO) less than 60% predicted.
Left ventricular ejection fraction: less than 40%.
Transaminases greater than 5x upper limit of normal
Psychiatric disorder or mental deficiency severe enough as to make compliance with the BMT treatment unlikely, and making informed consent impossible.
Major anticipated illness or organ failure incompatible with survival from PBSC transplant.
Pregnant or lactating
(any of the following would exclude the donor from participating)
Pregnant or lactating
Donor unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of congestive heart failure or unstable angina, thrombocytopenia)
HIV positive
Hemoglobin SS, SC, or Sbeta thal0, or beta thalassemia intermedia
Abnormal Red Cell Adenosine Deaminase level

Location and Contact Information

      National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222 
TTY  1-866-411-1010 

More Information

Detailed Web Page


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Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44.

Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. 1995 May 18;332(20):1317-22.

Study ID Numbers:  030170; 03-DK-0170
Record last reviewed:  May 25, 2004
Last Updated:  March 30, 2005
Record first received:  May 29, 2003 Identifier:  NCT00061568
Health Authority: United States: Federal Government processed this record on 2005-04-08

Cache Date: April 9, 2005